Borrelia burgdorferi, the Lyme disease spirochete, is maintained within a complex enzootic life cycle involving the tick vector and the mammal. The spirochete adapts to these diverse environments, in part, by selective gene expression. Environmental cues such as temperature, pH and nutrients influence in vitro B. burgdorferi gene expression. Analysis of the gene expression of lipoproteins in the infected murine skin has defined two remarkably different microenvironments for B. burgdorferi adaptation: naive status and immune status. In the naive state, B. burgdorferi expresses 116 of its lipoprotein genes while only 34 of them are expressed during chronic infection. B. burgdorferi is able to invade almost all organs and tissues of the mammalian host and these diverse microenvironments may influence its lipoprotein gene expression. This pathogen causes murine carditis and arthritis that parallel two major manifestations of human Lyme disease. It is unknown whether inflammation influences B. burgdorferi adaptation. In this project, the tissue differential expression of lipoprotein genes and the influence of inflammation on lipoprotein gene expression of B. burgdorferi will be investigated using the murine model. To achieve these goals, the following specific aims will be completed. 1. To investigate the tissue differential expression of B. burgdorferi lipoprotein genes in the bladder, heart and joint during murine infection; 2. To examine the influence of inflammation on B. burgdorferi adaptation.